Radiation-induced transformation of peptides into nanoparticles for nano-theranostics of pancreatic cancer with controllable drug delivery and sustained release

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Abstract
Nano-theranostics using biodegradable polymers are effective for the diagnosis and treatment of intractable cancers; however, there is a need for technology that controls bioavailability and biodegradability without compromising biocompatibility. In this study, peptide nanoparticles (NPs) with controlled particle size and biodegradability were prepared by ionizing radiation and loaded with imaging agents and anticancer drugs to develop novel nano-theranostics for pancreatic cancer diagnosis and treatment. Peptides composed of histidine, glycine, glutamic acid, and an arginine-glycine-aspartic acid motif were synthesized by the solid-phase synthesis method. Their aqueous solutions were irradiated with γ-rays to produce NPs with a particle size of less than 50 nm, enabling penetration of the pancreatic cancer stroma. The radiation crosslinking of peptides, with or without the arginine-glycine-aspartic acid motif, in water was investigated by pulse radiolysis. Peptide NPs loaded with fluorescent labeling or magnetic resonance imaging agents were efficiently taken up by pancreatic cancer cells. Cisplatin-loaded peptide NPs produced by higher-dose irradiation suppress drug-release rates owing to their lower biodegradability. In conclusion, peptide NPs with controllable particle size and biodegradability were produced by ionizing radiation and loaded with fluorescent labeling agents, magnetic resonance imaging agents, and anticancer drugs to develop a new nano-theranostics drug for pancreatic cancer diagnosis and treatment.
Funding Information
  • Innovative Science and Technology Initiative for Security, ATLA, Japan
  • Japan Society for the Promotion of Science
  • Japan Society for the Promotion of Science.

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